New insights into blood flow fluctuations offer hope in the fight against cardiovascular disease

Researchers have discovered how fluctuations in blood flow that occur when arteries narrow contribute to harmful inflammation and blood clot formation, highlighting the critical role that blood flow-related forces play in the development and progression of cardiovascular disease.

These new findings by researchers at the Baker Heart and Diabetes Institute, published today (22 August) in Nature communicationhave led to the identification of a target that could curb harmful inflammation and blood clot formation, potentially having a significant impact on diseases such as atherosclerosis and heart valve disease.

When blood vessels narrow, blood flow fluctuates and a series of cellular events occur, including the activation of white blood cells – the body's innate immune response.

However, the fluctuation in blood flow (shear stress) also triggers a process called NETosis, in which white blood cells (neutrophils) release net-like structures that trap and neutralize harmful invaders such as bacteria. This trapping and resulting arterial plaque has been found to contribute to harmful inflammation and blood clot formation.

Sara Baratchi, director of the Mechanobiology and Microfluidics Laboratory at the Baker Institute, has discovered that an ion channel called Piezo1 is critical to the NETosis process, paving the way for the development of protective treatments to prevent shear stress-induced artery narrowing.

“Our research has found that Piezo1 senses the stress caused by the fluctuations in blood flow, leading to an influx of calcium. This in turn triggers NETosis and the formation of these white blood cell traps, as well as the harmful inflammation and clot formation that follows,” she said.

“Targeting the Piezo1 ion channel could be a promising therapeutic strategy to curb harmful inflammation and blood clot formation, with significant potential public health benefits.”

Atherosclerosis is a narrowing of the arteries caused by the buildup of fats, cholesterol and other substances in and on the artery walls, and is the cause of about 50% of all deaths in Western society. It can lead to strokes, heart attacks, dementia and other health problems.

“Blood flow-driven forces such as shear stress play a critical role in the development and progression of various cardiovascular diseases, including atherosclerosis and valvular heart disease,” said Sara.

“Understanding the effect of shear stress in areas where blood vessels or heart valves are constricted due to immune cells is critical in the context of cardiovascular disease as it provides important insights into the mechanisms driving disease progression and complications.

“With these findings, we are one step closer to identifying protective treatments that can prevent this harmful blood clotting caused by the NETosis process.”

Provided by Baker Heart and Diabetes Institute